Catalytic processes are indispensable in the chemical industry. Frequently, catalytic processes employ a catalyst that is incorporated on a support. Effective use of the catalyst often corresponds to the quality of the catalyst support. Poor quality catalyst supports, due to at least one of poor structure, physical degradation, chemical degradation, undesirable properties, and inconsistent properties, limit the effectiveness of catalysts incorporated therein. Conditions such as high temperatures, high pressures, and high or low pH environments present challenges to the integrity of catalyst supports.
Palladium catalysts are employed in synthetic organic chemistry, particularly in the pharmaceutical industry, for debenzylation. Commercially available palladium debenzylation catalysts are made on a carbon support having a surface area below 1,000 m2/g, wherein about 50% of the surface area is located in micro pores (below 20 Å). Such carbon supports also have a ratio of micro pore volume to total pore volume of 20% or more.
Non-carbon catalyst supports are employed in catalytic processes in attempts to overcome the disadvantages associated with conventional carbon supported catalysts. Non-carbon supports include alumina supports, silica supports, alumina-silica supports, various clay supports, titania, and zirconium supports. However, there are at least one of two disadvantages associated with non-carbon catalyst supports; namely, that they may loose physical strength, and that they are dissolved in corrosive environments (such as acidic solutions).
Debenzylation involves separating a benzyl group from a functional group. One attractive use for debenzylation is cleaving a benzyl protective group from an amino or hydroxy functional group during organic synthesis. For example, during the synthesis of a multifunctional organic compound, reactive sites must be temporarily blocked until completion of the compound. Otherwise, reactive sites such as amino or hydroxy functional groups undesirably participate in reactions designed to create the compound of interest. Benzyl groups are consequently often employed as protective groups to prevent unwanted reactions.
The effectiveness and usefulness of a given protective group is determined, in part, by the ease in which it can be attached and subsequently removed from the organic compound being synthesized. Using conventional palladium debenzylation catalysts, it is sometimes difficult to reach a sharp end point for deprotection using benzyl protective groups. As a result, synthetic organic chemists sometimes select non-catalytic techniques for deprotection.
The effectiveness and usefulness of a given protective group is also determined, in part, by the selectivity associated with deprotection (removal of the protective group from the compound of interest). There are two notable aspects to selectivity.
First, in some instances, the same protective group may be employed to protect two or more different functional groups. Selectivity thus refers to the ability to remove the protective group from one functional group without removing it from another, different functional group. For example in organic synthesis, it may be desirable to cleave a first benzyl protective group from an amino functional group while not cleaving a second benzyl protective group from a hydroxy functional group located at a different position on the compound of interest.
Second, selectivity may refer to the ability to remove the protective group from a functional group without causing any unwanted side reactions. In this connection, deprotection using palladium debenzylation catalysts involves hydrogenolysis of the benzyl protective group. However, hydrogenolysis may hydrogenate a number of functional groups that may be present in the organic compound of interest. Groups such as C═C, C≡C, C≡N, —RNO2, -aryl-halogen, and the like can be hydrogenated under relatively mild conditions using palladium catalysts.
Finally, the effectiveness and usefulness of a given protective group is determined, in part, by cost considerations. Deprotection of amine groups often requires relatively large amounts of palladium catalyst. This coupled with the high cost of palladium metal, sometimes works to disfavor the use of palladium catalysts.